Control of the pathology of discogenic low back pain by regulating micro-inflammation

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09609
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Endo Kenji 東京医科大学, 医学部, 准教授 (90266479)
• Co-Investigator(Kenkyū-buntansha): 山本 謙吾 東京医科大学, 医学部, 主任教授 (10246316) ; 澤地 恭昇 東京医科大学, 医学部, 講師 (20571152) ; 鈴木 秀和 東京医科大学, 医学部, 兼任講師 (40317871) ; 高松 太一郎 東京医科大学, 医学部, 助教 (90459561)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 椎間板性疼痛 / interleukin-1 / autocrine / MAP kinase / DUSP1

Outline of Final Research Achievements

The pathological process of intervertebral discogenic pain involves a chronic micro-inflammation. IL-1α/β is a proinflammatory cytokine believed to play an important role in chronic microinflammatory conditions and its bioactivity is regulated by a balance with the endogenous inhibitory protein, IL-1Ra. However, the regulatory mechanisms of these three molecules are unknown.
In this study, we aimed to elucidate the mechanism by which IVD forms a chronic micro-inflammatory condition through autocrine-like positive feedback mechanisms of IL-1 derived from IVD cells themselves or neighboring cells. Furthermore, we focused on MAP kinases and their dephosphorylating enzyme, DUSP1, investigating the possibility in the control of this process, with the goal of exploring new treatment of the disease.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

本研究は，椎間板性疼痛の病態形成過程に慢性的な微小炎症状態が継続することに着目し，微小炎症形成に炎症性サイトカインであるIL-1α/βのautocrine様positive feedback機構が関与すること，またその制御に炎症刺激の細胞内情報伝達経路を担うMAP kinaseが関与すること，さらに同機構がMAP kinaseの脱リン酸化酵素であるDUSP-1により抑制できる可能性を明らかにした学術的意義の高い研究である．
また本研究成果は，椎間板性疼痛のみならず他の慢性運動器疼痛疾患への応用も強く期待され，社会的意義も高いと言える．